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W J Sandborn

Publications and source records attributed to W J Sandborn.

At least 91 records · Page 5Linked to original sources
PubMed1999

Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study.

Currently, no accepted medical therapy for patients with primary sclerosing cholangitis (PSC) is available. Case-control studies have shown an inverse association between PSC and smoking behavior, suggesting that nicotine might have a beneficial effect in PSC. The aim of this study was to evaluate the safety and estimate the efficacy of oral nicotine in the treatment of PSC. Eight PSC patients who had never smoked received oral nicotine at a maximum dose of 6 mg four times a day for up to one year. Liver biochemistries and plasma cotinine levels were determined at entry and at three-month intervals during the study duration. Five patients completed one year of treatment, but three of them had to temporarily reduce the dose due to side effects. One patient completed only four months of treatment due to dizziness and heart palpitations. Two patients completed only one month of treatment due to reactivation of colitis requiring corticosteroid therapy. No significant changes in liver biochemistries were noted during the treatment period despite a significant increase in plasma cotinine levels. In conclusion, oral nicotine seems to have no beneficial effects in the treatment of PSC, and it is frequently associated with side effects necessitating permanent drug cessation.

Administration, Oral↗
PubMed1999

A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known. AIM: To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome. METHODS: A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels. RESULTS: After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity. CONCLUSIONS: For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.

Adult↗
PubMed1999

Successful management of Crohn's disease of the ileoanal pouch with infliximab.

This study reports the clinical benefit and safety of the murine chimeric anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab, in the treatment of patients who developed findings compatible with Crohn's disease after undergoing colectomy with ileal-pouch anal anastomosis (IPAA) for an original diagnosis of ulcerative colitis. Medical records of 7 patients with Crohn's disease and an IPAA treated with infliximab were reviewed. Clinical response was classified as complete response, partial response, and no response. Concurrent treatment with immune modifier agents and/or antibiotics was recorded. Seven patients with active inflammatory or fistulizing Crohn's disease and an IPAA performed for diagnosis of ulcerative colitis were treated with infliximab after they had no response to conventional therapies. Patients received 1-4 infliximab infusions at a dose of 5 mg/kg. All patients improved clinically. Six patients had a complete response, and 1 had a partial response. Four of the 5 patients with complex perianal and fistulizing disease had closure of all fistula tracts, and 1 patient improved temporarily. Six of the 7 patients underwent concurrent treatment with immune modifier drugs. One patient had myalgias and malaise after the first infliximab infusion and flu-like symptoms after the second one. No other adverse effects were observed. This case series demonstrates that the murine chimeric anti-TNF-alpha monoclonal antibody, infliximab, can be used successfully to treat patients with Crohn's disease involving an IPAA who are refractory to conventional therapies.

Adult↗
PubMed1999

Medical therapy for induction and maintenance of remission in pouchitis: a systematic review.

OBJECTIVE: To determine the effectiveness of medical therapy (including metronidazole, bismuth carbomer enemas, oral probiotic bacteria, butyrate suppositories, and glutamine suppositories) for inducing a response or for maintaining remission in pouchitis. SEARCH STRATEGY: Studies were selected using the MEDLINE data base (1966-December 1997), abstracts from major gastrointestinal meetings, and references from published articles and reviews. SELECTION CRITERIA: Four randomized controlled trials of medical therapy in adult patients with pouchitis were identified: two placebo controlled trials in active chronic pouchitis; one maintenance of remission trial comparing two active agents in chronic pouchitis; and one placebo-controlled maintenance of remission trial for chronic pouchitis. A single patient "n-of-1" trial for active chronic pouchitis was excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Extracted data were converted to 2 x 2 tables (response versus no response and medical therapy versus placebo or medical therapy versus medical therapy) and an odds ratio with 95% confidence intervals (CI) were determined as described by Cochrane and Mantel and Haenszel. In addition, the absolute risk reduction, relative risk reduction, and number needed to treat were determined. MAIN RESULTS: The odds ratios of inducing a response using oral metronidazole or bismuth carbomer foam enemas compared with placebo in active chronic pouchitis were 12.34 (95% CI 2.34-64.95) and 1.00 (95% CI 0.29-3.42), respectively. The odds ratio of maintaining remission in chronic pouchitis for oral probiotic bacteria (VSL-3) compared with placebo was 15.33 (95% CI 4.51-52.14). There was no difference in the odds ratio of inducing symptomatic remission and then maintaining symptomatic remission after discontinuing suppressive medical therapy for chronic pouchitis with glutamine suppositories compared with butyrate suppositories, 2.75 (95% CI 0.48-15.94). CONCLUSIONS: Metronidazole is an effective therapy for active chronic pouchitis. Bismuth carbomer foam enemas are not effective therapy for active chronic pouchitis. Oral probiotic therapy with VSL-3 is an effective therapy for maintaining remission in patients with chronic pouchitis in remission. There is no difference in maintenance of symptomatic remission in patients with chronic pouchitis treated with glutamine versus butyrate suppositories, and it is unknown whether glutamine and butyrate are equally effective or ineffective. Additional randomized, double-blind, placebo-controlled, dose-ranging clinical trials are needed to determine the efficacy of empiric medical therapies currently being used in patients with pouchitis.

Adult↗
PubMed1999

Concurrent inflammatory bowel disease and myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) may be associated with inflammatory bowel disease (IBD). We characterized the clinical features and outcomes of patients with concurrent IBD and MDS. Using a diagnostic index, we identified all patients with both IBD and MDS at our center between 1976 and 1997. We also calculated an incidence rate of MDS in IBD using population-based data from Olmsted County, Minnesota, between 1950 and 1993. Among approximately 15,000 IBD patients seen, 25 (approximately 0.17%) were diagnosed with MDS. Fourteen had Crohn's disease and 11 had ulcerative colitis. The median age at diagnosis of IBD, particularly Crohn's disease, was higher than expected. Median age at diagnosis of MDS was typical. All but one ulcerative colitis patient was diagnosed before the diagnosis of MDS, while one-half of Crohn's disease patients were diagnosed with both ailments simultaneously. Five patients who had been diagnosed with IBD first were persistently anemic for at least 1 year prior to diagnosis of MDS. Two Crohn's disease patients had received purine analogs in the past. Median follow-up after MDS diagnosis was 1 year. Seven patients died, including two who progressed to acute myeloid leukemia. The incidence rate of MDS in IBD based on Olmsted County data was 0 cases per 100,000 person-years (95% CI, 0-55.2). The seemingly high frequency of myelodysplastic syndromes in a large referral-based group of patients with IBD suggests an association; however, an increased risk of MDS was not observed in a small regional cohort of IBD patients. Patients with MDS are diagnosed with concurrent IBD at an age older than expected. Simultaneous diagnoses were made in one-half of Crohn's disease patients. MDS should be considered in the differential diagnosis of anemia in IBD patients.

Aged↗
PubMed1999

Perinatal exposure to measles virus is not associated with the development of inflammatory bowel disease.

It has been suggested that early exposure to measles virus, including perinatal exposure via maternal infection, may lead to persistent measles virus infection and the subsequent development of inflammatory bowel disease (IBD). We sought to examine this association in our patient population. Maternal measles infection was identified through the Mayo Clinic diagnostic index, and cases were verified by chart review. Cases were included if infection occurred between the second trimester and 6 months postpartum. The offspring, or a first degree family member, were then interviewed regarding a history of IBD or symptoms which might suggest IBD. Seven cases of maternal infection were identified out of 67,912 pregnancies between 1935 and 1985. One offspring was lost to follow-up through adoption, and the remaining six have no evidence of Crohn's disease or ulcerative colitis after a mean of 38 years of follow-up (range 12-62 years). Evidence for an association between perinatal exposure to measles virus via maternal infection and the subsequent development of IBD was not found in our patient population.

Colitis, Ulcerative↗
PubMed1999

Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety.

Tumor necrosis factor-alpha (TNFalpha), a proinflammatory cytokine, plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Biotechnology agents including a chimeric monoclonal anti-TNF antibody (infliximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombinant TNF receptor fusion protein (etanercept) have been used to inhibit TNFalpha activity. Controlled trials have demonstrated efficacy for infliximab in moderately to severely active Crohn's disease (CD) and fistulizing CD sufficient to justify recent U.S. Food and Drug Administration (FDA) approval. Additional trials have been completed in rheumatoid arthritis (RA). Similarly, preliminary controlled trials have suggested efficacy for CDP571 in active CD and RA. Larger controlled trials have demonstrated efficacy for etanercept in RA patients who have failed disease modifying antirheumatic drug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with anti-TNF therapies have included formation of human antichimeric antibodies (HACA) with associated acute and delayed hypersensitivity infusion reactions, human antihuman antibodies (HAHAs), and formation of autoantibodies with rare instances of drug-induced lupus. Several cases of non-Hodgkin's lymphoma also has been described. Future studies should evaluate optimal timing and duration of anti-TNF therapy, the utility of adjuvant medical treatments during anti-TNF therapy, and evaluate long-term safety and efficacy of the various anti-TNF agents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Plasma and rectal adenosine in inflammatory bowel disease: effect of methotrexate.

In animal models, the antiinflammatory mechanism of action of methotrexate has been attributed to elevation of the extracellular concentration of the endogenous autocoid, adenosine. Our goal was to determine if methotrexate elevates adenosine concentrations in plasma and at the site of disease in patients with inflammatory bowel disease. In 10 patients with Crohn's disease or ulcerative colitis, rectal adenosine and plasma adenosine concentrations were measured before and immediately after a subcutaneous injection of methotrexate, 15 or 25 mg. The mean predose rectal adenosine concentration of 2.4 mumol/l was not significantly different from the postdose concentration of 2.1 mumol/l, p = 0.17, (paired two-tailed t test). Rectal adenosine concentration tended to correlate with rectal endoscopic disease activity, r = 0.59, p = 0.067 (Spearman rank order correlation). After methotrexate injection, neither the mean daily plasma adenosine concentration, nor the plasma adenosine at any individual time point, were significantly different from preinjection values. In patients with inflammatory bowel disease, an injection of methotrexate in the clinically effective dose range does not raise rectal or plasma adenosine concentrations. A role for adenosine as the mediator of the antiinflammatory action of methotrexate is not supported.

Adenosine↗
PubMed1999

Transdermal nicotine decreases mucosal IL-8 expression but has no effect on mucin gene expression in ulcerative colitis.

Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.

Administration, Cutaneous↗
PubMed1999

Combination therapy with oral tacrolimus (FK506) and azathioprine or 6-mercaptopurine for treatment-refractory Crohn's disease perianal fistulae.

Our aim was to report the clinical experience with combination treatment using tacrolimus and either azathioprine (AZA) or 6-mercaptopurine (6MP) in patients with Crohn's disease (CD) perianal fistulae. The medical records of all patients with Crohn's disease perianal fistulae seen at the Mayo Clinic from 1996-1998 who were treated with tacrolimus were reviewed. Clinical response was classified as: complete response, partial response, and nonresponse. Eleven patients were treated with oral tacrolimus for a mean duration of 22 weeks. The initial oral dose of tacrolimus ranged from 0.15 to 0.31 mg/kg/day. Azathioprine or 6MP was continued in combination with tacrolimus in seven patients and initiated simultaneously with tacrolimus in four patients. All patients improved clinically, seven had a complete response, and four had a partial response. The mean time to initial improvement was 2.4 weeks, and the mean time to complete response was 12.2 weeks. The most frequent adverse events were nausea, paresthesias, nephrotoxicity, and tremor. Patients with nephrotoxicity had a significantly higher mean initial tacrolimus dose (0.31 mg/kg/day) compared with patients who did not have nephrotoxicity (0.25 mg/kg/day) (p = 0.035); however, there was not a statistically significant association between the starting dose or mean blood level and clinical response. Combination therapy with oral tacrolimus and AZA or 6MP may be effective treatment for CD perianal fistulae. Higher initial tacrolimus doses increase the risk of nephrotoxicity without improving clinical response.

Administration, Oral↗
PubMed1999

Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results.

Smoking is protective against developing ulcerative colitis. Nicotine may be the cause of this protective effect. Controlled trials have demonstrated efficacy of transdermal nicotine for active ulcerative colitis. Side effects observed with transdermal nicotine include contact dermatitis, nausea, and lightheadedness. Topical administration of nicotine to the colon reduces nicotine blood concentrations and side effects, and may be of clinical benefit.

Colitis, Ulcerative↗
PubMed1999

Practice guidelines for inflammatory bowel disease: an instrument for assessment.

The development of practice guidelines is problematic because guidelines that are too broad have no value and guidelines that are highly specific cannot address the nuances of every patient's illness. In this article, we present the hypothesis that practice guidelines that provide specific objectives for assessment and intervention in inflammatory bowel disease can be used to measure practice variation. These guidelines are proposed as 15 specific objectives with options for intervention. These objectives could be used as an instrument to quantify variations in clinical practice and to assess the benefits of practice guidelines.

Diagnosis, Differential↗
PubMed1998

Primary sclerosing cholangitis and colorectal carcinoma in patients with chronic ulcerative colitis: a case-control study.

BACKGROUND: Controversy persists regarding primary sclerosing cholangitis (PSC) as a risk factor for colorectal carcinoma in patients with chronic ulcerative colitis. Small sample size and differing endpoints have contributed to variation among reported studies. This large case-control study was conducted to examine the possible association between PSC and colon carcinoma in patients with ulcerative colitis. METHODS: From Mayo Clinic records spanning 1976-1994, 171 cases with both ulcerative colitis and colorectal carcinoma and 171 contemporaneous controls with ulcerative colitis but no colorectal neoplasia matched with regard to age, gender, extent, and duration of colitis were identified. The diagnosis of PSC required cholangiographic confirmation. Analysis employed a multivariate logistic regression model. RESULTS: The prevalence of PSC was similar in cases (18%) and controls (15%) (P = 0.54). The adjusted odds ratio for colorectal carcinoma with PSC was 1.23 (95% confidence interval, 0.62-2.42). CONCLUSIONS: Based on this large case-control study, there was no association between PSC and colorectal carcinoma in patients with ulcerative colitis.

Adolescent↗
PubMed1998

Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation.

Several centers have identified colorectal cancer in patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) who have undergone orthotopic liver transplantation. Increased frequency of surveillance colonoscopy and prophylactic colectomy has been recommended. To address these concerns, we reviewed the posttransplantation experience with colorectal neoplasia in patients with PSC and UC at our institution. All patients with PSC and UC who underwent liver transplantation at Mayo Clinic between April 1985 and December 1993 were followed up through their complete history for colorectal dysplasia, cancer, or death. Eighty-one of 108 patients with PSC (75%) had concomitant inflammatory bowel disease (all but 1 had UC). Proctocolectomy had been performed before transplantation in 24 (30%). Median follow-up after transplantation was 4.2 years. Among the 57 patients with intact colons, 3 developed colorectal cancer, an incidence of approximately 1% per person per year. The cumulative incidence of dysplasia was 15% at 5 years and 21% at 8 years. Overall actuarial survival stratified by presence or absence of an intact colon at transplantation was similar (86% and 86%, respectively, at 5 years). The risk of carcinoma after transplantation compared with that expected for patients during a comparable (pretransplantation) period was increased fourfold but was not statistically significant. The risk of colorectal neoplasia (dysplasia and cancer) after liver transplantation in patients with PSC and UC is clinically important. However, this risk had no impact on patient survival. Prophylactic proctocolectomy does not appear necessary, but annual surveillance colonoscopy is recommended.

Cholangitis, Sclerosing↗
PubMed1998

Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival.

BACKGROUND & AIMS: Many centers worldwide have reported an increased incidence of Crohn's disease, but population-based data in North America are sparse. We studied the incidence and prevalence of Crohn's disease in Olmsted County, Minnesota, and examined temporal trends in incidence and survival. METHODS: Residents diagnosed with Crohn's disease between 1970 and 1993 were incidence cases, and residents with Crohn's disease who were alive on January 1, 1991, were prevalence cases. Cases from previous studies were reconfirmed. Rates were adjusted using 1990 U.S. Census figures for whites. Incidence trends were evaluated with a Poisson regression model. Survival from diagnosis was compared with that expected for U.S. north-central whites. RESULTS: Between 1940 and 1993, 225 incidence cases were identified, for an adjusted incidence rate of 5.8 per 100,000 person-years. On January 1, 1991, there were 145 residents with Crohn's disease, an adjusted prevalence rate of 133 per 100,000, 46% higher than that seen in 1980. Incidence rates before 1964 were significantly lower than those of 1989-1993. Observed survival was less than expected (P = 0.007). CONCLUSIONS: The incidence of Crohn's disease has stabilized since the 1970s at a rate higher than that seen previously. Prevalence has increased by 46% since 1980. Overall survival is slightly decreased.

Adolescent↗